AB0324 SAFETY PROFILE OF JAK INHIBITORS IN REAL WORLD FROM A SINGLE CENTER COHORT
Authors: R. González Mazarío, J. J. Fragío Gil, L. Mas Sanchez, P. Muñoz Martinez, F. Ortiz-Sanjuán, C. Pávez Perales, S. Leal Rodriguez, C. Riesco Barcena, A. V. Huaylla Quispe, M. De la Rubia Navarro, L. Gonzalez Puig, E. Grau García, J. E. Oller Rodríguez, I. Martínez Cordellat, R. Negueroles Albuixech, E. Vicens Bernabeu, J. Ivorra Cortés, C. Nájera Herranz, I. Cánovas Olmos, J. A. Román Ivorra
Journal: Annals of the Rheumatic Diseases (2022)

Background Recent published data have emerged some concerns about safety of Janus kinase (JAK) inhibitors and FDA have established prescribing restrictions. Objectives The aim of this study was to analyze the safety profile of current approved JAK inhibitors in Europe with data from a Real World cohort. Methods A single center observational study was performed including patients who had initiated treatment with Tofacitinib, Baricitinib or Upadacitinib from September, 2017 to January, 2022. Demographic, clinical, laboratory and safety variables were collected from baseline and at months 1, 3, 6 and every six months. Safety data was collected including any adverse event (AE) due to any cause. An AE was considered serious if it was life-threatening or result in hospitalization, disability or in death. All AE and SAE were expressed adjusted by exposure (E/100 PY). Results A total of 194 patients were included whom baseline demographic and disease characteristics are exposed in Table 1. Drug exposure was 265.5 patient-years. Overall, 214 AE were detected being mild upper tract respiratory infection the most frequently registered (15.82 E/100PY) followed by Urinary tract Infection accounting 7.16 E/100PY. 10 Serious Infections were detected in 10 patients of which 5 were pneumonia (1.88 E/100PY), 1 cellulitis (0.38 E/100PY) and 2 COVID-19 (0.76 E/100PY). 12 herpetic infection were detected in 9 patients (4.52 E/100PY) of which 7 were caused by herpes zoster (2.64 E/100PY) and 5 by herpes simplex (1.88 E/100PY) 3 cases were mono-metameric and 4 multi-metameric. Moreover, 2 patient developed postherpetic neuralgia. A patient with RA developed Miliary Tuberculosis (0.38 E/100PY) with a negative IGRA test prior to the JAKi. A patient with RA suffered a Myocardial Infarction (0.38 E/100PY). 7 RA patients developed malignancy (2.64 E/100PY), one with oral squamous cell carcinoma, two Bowen carcinoma, one breast cancer, 2 basal cell carcinoma and a colorectal metastatic cancer. Not a single case of thromboembolic event nor Hepatitis B Virus reactivation were registered. 2 patients died, one with cancer and the other suffered a severe COVID-19 (unvaccinated). Table 1. DEMOGRAPHIC, DISEASE AND TREATMENT BASELINE CHARACTERISTICS. Characteristic Rheumatoidarthritis n=163 (84.02%) Psoriatic arthritis n=18 (9.28%) Juvenile idipathic arthritis n=7 (3.61%) Other n=6 (3.09%) Age - years 55.23 (16.84) 54.71 (11.89) 27.14 (5.18) 48 (12.95) Female sex – number (%) 142 (87.12) 12 (66.66) 6 (85.71) 4 (66.67) Race – number (%) Caucasian 135 (82.82) 16 (88.89) 7 (100) 6 (100) Asian 2 (1.23) 0 (0) 0 (0) 0 (0) Latin 26 (15.95) 2 (11.11) 0 (0) 0 (0) Comorbidities – number (%) High blood pressure 118 (72.39) 11 (61.11) 0 (0) 0 (0) Dyslipemia 54 (33.13) 6 (33.33) 0 (0) 1 (16.67) Diabetes Mellitus 10 (6.13) 3 (16.66) 0 (0) 1 (16.67) Positive HBV serology 12 (7.36) 1 (5.55) 0 (0) 0 (0) Latent Tuberculosis 15 (9.20) 1 (5.55) 0 (0) 0 (0) JAKi Baricitinib 61 (37.42) 0 (0) 2 (28.57) 1 (16.67) Tofacitinib 83 (50.92) 15 (83.33) 4 (57.14) 3 (50) Upadacitinib 19 (11.66) 3 (16.67) 1 (14.29) 2 (33.33) Patients taking glucocorticoids – number (%) 112 (68.71) 9 (50) 3 (42.86) 1 (16.67) Conclusion In this updated analysis of 194 patients treated with JAKi, the three approved JAKi showed a safety profile consistent with data from RCT. The patients under JAK therapy should be carefully evaluated on their follow-up. Disclosure of Interests None declared